Establishing structure-function correlations is fundamental to understanding how information is processed in the central nervous system (CNS). Axonal connectivity is a key relationship that facilitates information transmission and reception within the CNS. Recently, diffusion weighted magnetic resonance imaging (DW-MRI) methods have been shown to provide fundamental information required for viewing structural connectivity and have allowed visualization of fiber bundles in the CNS in vivo. In this project, we propose to develop methods for extraction and analysis of these patterns from high angular resolution diffusion weighted images (HARDI) that is known to have better resolving power over diffusion tensor imaging (DTI). To this end, a biologically relevant and clinically important model has been chosen to study changes in the organization of fibers in the intact and injured spinal cord. Our hypothesis is that, changes in geometrical properties of the anatomical substrate, identifying the region of injury and neuroplastic changes in distant spinal segments, correlate with different magnitudes of injury and levels of locomotor recovery following spinal cord injury (SCI). Prior to hypothesis testing, we will denoise the HARDI data and then construct a normal atlas cord. Deformable registration and tensor morphometry between a normal atlas and an injured cord would be performed to provide a distinct signature for each type of behavior recovery associated with the SCI substrate. Validation of the hypothesis will be performed through systematic histological analysis of cord samples following acquisition of the HARDI data. Spinal cords will be cut and stained with fiber and cell stains to verify changes in anatomical organization that result from contusive injury (common in humans as well) to the spinal cord. A comparison between anatomical characteristics obtained from histological versus HARDI analysis will provide validation for the image analysis and the hypothesis. Three severities of spinal cord injuries will be produced (light, mild and moderate contusions) based upon normed injury device parameters. The structural signatures of these labeled data subsets will then be identified. Automatic classification of novel & injured cord HARDI data sets will then be achieved using a large margin classifier. Finally, HARDI data acquired over time will be analyzed in order to learn and predict the level of locomotor recovery by studying the structural changes over time and developing a dynamic model of structural transformations corresponding to each chosen class. We will use an auto-regressive model in the feature space to track and predict structural changes in SCI and correlate it to functional recovery. PUBLIC HEALTH RELEVANCE: This project involves the development of automated methods to extract morphological signatures that characterize changes in spinal cord injury (SCI) substrate estimated from Diffusion MRI scans of rats, and predict the functional recovery by correlating to behavioral studies. Although the various algorithms developed here are for analysis of SCI, they can be used in other applications such as traumatic brain injury, in tracking and predicting developmental changes etc. from diffusion MRI scans.